Transgenic mice offer an excellent model system to study the molecular mechanisms of gene regulation during development. Using transgenic animal models, biological functions of genes can be studied in the context of the whole organism. Moreover, heterologous promoters can be used to study the effect of selected genes in different cells or tissue types. In this study, we propose to develop ets-1 and ets-2 transgenic mice to investigate the biological functions of these transcription factors in vivo. In addition, to study the tissue-specific function and regulation of the ets genes in the growth and development of normal and ets transgenic mice, the ets-2 transgenic mice were generated by utilizing mouse and sheep metallothionein promoters. The ets-2 transgenic mice have dome-shaped heads and develop skeletal deformities such as osteomalacia. Previously, we have demonstrated that the ets-1 is expressed in developing bone during murine embryogenesis, including vertebrae, developing limbs and other sites where bone development occurs, suggesting that ets family transcription regulates bone-specific genes. Osteopontin (OPN) is a major non-collagenous bone matrix protein. Although the promoter has been cloned, the regulation of OPN gene has not been studied in detail during development of bone cells or in mature osteoblasts. We examined the OPN promoter and found that it contains various ets binding sites; thus, it is possible that this bone-specific gene is regulated by ets-1.